title: Anthricin Isolated from Anthriscus sylvestris (L.) Hoffm. Inhibits the Growth of Breast Cancer Cells by Inhibiting Akt/mTOR Signaling, and Its Apoptotic Effects Are Enhanced by Autophagy Inhibition.
abstract: Anthricin (deoxypodophyllotoxin) is a natural product isolated from Anthriscus sylvestris (L.) Hoffm. (Apiaceae). Here, we investigated the effect of anthricin on autophagy and mammalian target of rapamycin (mTOR) signaling as anticancer actions in breast cancer cells. Many studies have supported the contention that the phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 pathway is considerably deregulated in breast cancer and that autophagy plays important roles in the development of this type of cancer, although the exact underlying mechanisms remain unknown. Our data confirmed that anthricin markedly induced apoptosis in 2 breast cancer cell lines, MCF7 (estrogen receptor positive) and MDA-MB-231 (estrogen receptor, progesterone receptor, and Her2/Neu receptor negative). Anthricin treatment decreased the levels of phosphorylated Akt and mTORC1, followed by inhibition of cell growth. Interestingly, blockage of autophagy by a pharmacological inhibitor or genetic deletion of ULK1 and Atg13 accelerated anthricin-induced apoptosis, suggesting that autophagy has cytoprotective effects. Taken together, our results indicate that anthricin is an inhibitor of mTOR and that a combination of an autophagy inhibitor and anthricin may serve as a new promising strategy for the treatment of breast cancer cells.
authors.affiliation: Department of Food Biotechnology, University of Science and Technology, Daejon 305-806, Republic of Korea ; Division of Metabolism and Functionality Research, Korea Food Research Institute, 1201 Anyangpangyo-ro, Seongnam 463-746, Republic of Korea.
authors.forename: Chang Hwa
authors.initials: CH
authors.lastname: Jung
authors.forename: Heemun
authors.initials: H
authors.lastname: Kim
authors.forename: Jiyun
authors.initials: J
authors.lastname: Ahn
authors.forename: Sung Keun
authors.initials: SK
authors.lastname: Jung
authors.forename: Min Young
authors.initials: MY
authors.lastname: Um
authors.forename: Kun-Ho
authors.initials: KH
authors.lastname: Son
authors.forename: Tae Wan
authors.initials: TW
authors.lastname: Kim
authors.forename: Tae Youl
authors.initials: TY
authors.lastname: Ha